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FBW7-mediated ubiquitination and degradation of KLF5 被引量:6
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作者 Yi Luan Ping Wang 《World Journal of Biological Chemistry》 CAS 2014年第2期216-223,共8页
Krüppel-like factor(KLF) family proteins are transcription factors that regulate numerous cellular functions, such as cell proliferation, differentiation, and cell death. Posttranslational modification of KLF pro... Krüppel-like factor(KLF) family proteins are transcription factors that regulate numerous cellular functions, such as cell proliferation, differentiation, and cell death. Posttranslational modification of KLF proteins is important for their transcriptional activities and biological functions. One KLF family member with important roles in cell proliferation and tumorigenesis is KLF5. The function of KLF5 is tightly controlled by post-translational modifications, including SUMOylation, phosphorylation, and ubiquitination. Recent studies from our lab and others' have demonstrated that the tumor suppressor FBW7 is an essential E3 ubiquitin ligase that targets KLF5 for ubiquitination and degradation. KLF5 contains functional Cdc4 phospho-degrons(CPDs), which are required for its interaction with FBW7. Mutation of CPDs in KLF5 blocks the ubiquitination and degradation of KLF5 by FBW7. The protein kinase Glycogen synthase kinase 3β is involved in the phosphorylation of KLF5 CPDs. In both cancer cell lines and mousemodels, it has been shown that FBW7 regulates the expression of KLF5 target genes through the modulation of KLF5 stability. In this review, we summarize the current progress on delineating FBW7-mediated KLF5 ubiquitination and degradation. 展开更多
关键词 Kr�fc ppel-like factor 5 FBW7 Ubiquitin proteasome system degradation Kr�fc ppel-like factor family
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MG-132提高TNFR-Fc融合蛋白在CHO细胞中表达的研究 被引量:2
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作者 温家明 聂艳峰 +5 位作者 梁翰章 黄雯茜 雷云 谢秋玲 裴运林 熊盛 《中国生物工程杂志》 CAS CSCD 北大核心 2015年第9期1-6,共6页
目的:在不影响细胞活力的前提下,通过抑制人肿瘤坏死因子受体-Fc(TNFR-Fc)融合蛋白的降解,提高其在中国仓鼠卵巢(CHO)细胞中的产量和质量。方法:通过在细胞培养过程中加入全蛋白质合成抑制剂Cycloheximide、溶酶体抑制剂Leupeptin、蛋... 目的:在不影响细胞活力的前提下,通过抑制人肿瘤坏死因子受体-Fc(TNFR-Fc)融合蛋白的降解,提高其在中国仓鼠卵巢(CHO)细胞中的产量和质量。方法:通过在细胞培养过程中加入全蛋白质合成抑制剂Cycloheximide、溶酶体抑制剂Leupeptin、蛋白酶体抑制剂MG-132,验证TNFR-Fc融合蛋白在CHO细胞的降解途径;免疫印迹(Western blot)方法检测在细胞内TNFR-Fc融合蛋白的变化,酶联免疫吸附试验(ELISA)方法检测分泌表达的TNFR-Fc融合蛋白的含量。Protein A亲和层析纯化细胞培养液上清,高效液相色谱(HPLC)检测重组蛋白的纯度,并通过阻断肿瘤坏死因子α(TNFα)诱导的L929细胞毒作用来检测纯化的TNFR-Fc蛋白的活性。结果:TNFR-Fc在CHO细胞内,经泛素蛋白酶体途径降解,稳定表达TNFR-Fc的CHO细胞培养过程中添加50μmol/L MG-132,可以使TNFR-Fc融合蛋白的分泌表达量提高42.35%,纯化后,二聚体比例提高28.60%,并且纯化后目的蛋白的比活性也增加。结论:在不影响细胞活力、蛋白质生物学活性的前提下,添加蛋白酶体抑制剂MG-132提高TNFR-Fc融合蛋白在CHO细胞中的表达量,为进一步研究从抑制蛋白质降解途径来提高重组蛋白在CHO细胞中的表达量提供了现实依据。 展开更多
关键词 MG-132 TNFR-fc降解 CHO细胞 泛素化 提高表达
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Treatment technologies for aqueous perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) 被引量:28
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作者 Chad D.VECITIS Hyunwoong PARK +2 位作者 Jie CHENG Brian T.MADER Michael R.HOFFMANN 《Frontiers of Environmental Science & Engineering》 SCIE EI CSCD 2009年第2期129-151,共23页
Fluorochemicals(FCs)are oxidatively recalcitrant,environmentally persistent,and resistant to most conventional treatment technologies.FCs have unique physiochemical properties derived from fluorine which is the most e... Fluorochemicals(FCs)are oxidatively recalcitrant,environmentally persistent,and resistant to most conventional treatment technologies.FCs have unique physiochemical properties derived from fluorine which is the most electronegative element.Perfluorooctanesulfonate(PFOS),and perfluorooctanoate(PFOA)have been detected globally in the hydrosphere,atmosphere and biosphere.Reducing treatment technologies such as reverses osmosis,nano-filtration and activated carbon can remove FCs from water.However,incineration of the concentrated waste is required for complete FC destruction.Recently,a number of alternative technologies for FC decomposition have been reported.The FC degradation technologies span a wide range of chemical processes including direct photolysis,photocatalytic oxidation,photochemical oxidation,photochemical reduction,thermally-induced reduction,and sonochemical pyrolysis.This paper reviews these FC degradation technologies in terms of kinetics,mechanism,energetic cost,and applicability.The optimal PFOS/PFOA treatment method is strongly dependent upon the FC concentration,background organic and metal concentration,and available degradation time. 展开更多
关键词 fluorochemical(fc)degradation technologies perfluoroctanesulfonate(PFOS) PERFLUOROOCTANOATE (PFOA) oxidation reduction PHOTOLYSIS THERMOLYSIS review
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肾移植抗体介导排斥反应新型药物治疗的研究进展 被引量:1
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作者 杨洋 王志鹏 +6 位作者 张健 丁光璞 孙雯 张磊 林俊 朱一辰 田野 《中华泌尿外科杂志》 CAS CSCD 北大核心 2022年第12期948-952,共5页
抗体介导的排斥反应(antibody-mediated rejection,AMR)是影响肾移植受者和移植肾远期预后的首要因素。目前,尚无一种药物能被普遍认可或者获得批准用于AMR的治疗。因此,亟需开展更多的新型药物研究与临床试验,以期改变肾移植受者的长... 抗体介导的排斥反应(antibody-mediated rejection,AMR)是影响肾移植受者和移植肾远期预后的首要因素。目前,尚无一种药物能被普遍认可或者获得批准用于AMR的治疗。因此,亟需开展更多的新型药物研究与临床试验,以期改变肾移植受者的长期预后。基于预防和治疗AMR的核心原则,本文从清除供者特异性抗体、阻断抗体与补体介导的组织损伤、抑制产生抗体细胞的增殖与活化3个方面综述了目前最受关注的几类新型药物治疗AMR的作用原理与疗效。这些新兴药物已显示出在预防和治疗AMR、改善受者预后方面的潜力,有望在未来改变AMR治疗的 困局,为临床改善肾移植受者的长期预后提供更多有效的治疗选择。 展开更多
关键词 肾移植 抗体介导的排斥反应 IgG肽链内切酶 fc新生儿受体 托珠单抗
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